Description of Research Expertise

The May laboratory investigates signal transduction pathways that lead to altered patterns of gene expression in immune and inflammatory responses. We are particularly interested in understanding how the loss of control of normal signaling contributes to the progression of diseases such as chronic inflammation and cancer. Our goal is to determine the specific molecular events underlying aberrant signals and to define realistic targets for selectively blocking abnormal, while maintaining physiologically normal responses. The focus of our work is the Nuclear Factor (NF)-kappa B transcription factor activation pathway that is critical for inflammation, innate and adaptive immunity and lymphocyte development. NF-kappa B activation is typically a rapid and transient response, however constitutive NF- kappa B activity occurs at sites of chronic inflammation and in various tumors, leukemias and lymphomas. We combine cellular, molecular and genetic approaches to determine the mechanisms that redirect normal NF-kappa B activation pathways into this functionally abnormal, constitutively active state. In addition to determining the basic mechanisms of NF-kappa B activation we have a long-standing interest in understanding the role of NF-kappa B in regulating the phenotype and function of vascular endothelial cells.

A second related interest is to explore the experimental and therapeutic potential of peptide transduction technology as a strategy for modulating specific cell signaling responses. We previously described a small cell-permeable peptide inhibitor of NF-kappa B activity and demonstrated the feasibility of this approach both in vitro and in vivo. We will continue to exploit this exciting novel strategy to fully dissect deregulated NF-kappa B activity in chronic inflammatory diseases.